Membrane model of the regulation of proliferation: the theory and interpretation of an experiment

The role of cell surface physical organization in the cell cycle regulation is analyzed within the framework of the earlier proposed theory (Chernavskii et al., 1982). Two models of cell surface are considered: hard-frame fluid-mosaic model (latticemosaic) and the fluid-mosaic one. The former deals with normal cells. The existence of integral carcasse or "frame" which is formed by the essential part of cross-linked membrane components and may have at least two different conformational states is hypothesized. The second model describes membranes of tumour cells. With the latter theory any mitogen (excluding the restoration of nutrient depletion) reduces the mechanical tensile strength of the frame and stimulates the general structural rearrangement of the plasma membrane. There are only two conformational transitions during the cell cycle which serve as signals for the beginning of S and M phases. If the values of tensile strength are great enough and therefore the conformational transitions are impossible, the cells pass into the resting (prereplicative--G01, or premitotical--G02) state. Three types of experiments are interpreted in the proposed theory: a) on differences in the action of growth factors on normal and tumour cell cycle, b) on the necessary condition for mitogenicity of lectins, c) on the stimulation of proliferation by mechanical deformation of cells.     

Asymmetry of movement direction as a tactic in the feeding behavior of rats

The sign and degree of spatial-motor asymmetry in rats were studied in conditions both of spontaneous or signalled choice in an U-maze and spontaneous multiple choice in a radial labyrinth. It was shown that during investigation of a new environment, motor asymmetry in rats was feebly expressed in all conditions of experiments, irrespective of the labyrinth scheme and experimental procedures. In the process of training, adequate behaviour was formed and in some conditions a distinctly expressed spatial asymmetry appeared, while in other cases it was absent. Apparently, while investigating an "unknown" situation (where rats can move rightwards and leftwards), the strategy of "displacement" is characteristic of them. Later the rate of asymmetry manifestation depends on concrete spatial and temporal characteristics of already "familiar" surroundings.     

Correlation between the amplitude of action potentials and the rate of conduction along axons of the output cells of the sensomotor cortex

Antidromic responses of neighbouring neurones in micro-areas of the sensorimotor cortex to the stimulation of fibers of the pyramidal tract as well as of the red nucleus and thalamic nuclei VPL and MGB, were studied in acute experiments on unanesthetized immobilized cats. Depending on the velocity of conduction along the axon, the neurones of all the categories were divided into fast and slow cells. When examining the two neuronal groups most differing in AP amplitude (N1 and N3), it was found that N1 neurones were mainly fast-conducting and N3 neurones-- slow-conducting. The conclusion is made that at multineuronal recording, each of the examined categories of the output neurones is characterized by positive correlation between AP amplitude and the axon conduction velocity and consequently, the size of the cell.     

Effect of postsynaptic blockade of neuromuscualar transmission on properties of the frog fast muscle fiber membrane

Sensitivity of the postsynpatic membrane to acetylcholine, the resting membrane potential, input resistance, and membrane time constant of fast muscle fibers were measured in experiments on frogs. Complete immobilization of the animals with D-tubocurarine or local immobilization of a muscle with α-bungarotoxin was found not to affect these parameters of the muscle membrane, whereas denervation of the muscle widens the zone of postsynaptic sensitivity to acetylcholine, lowers the resting membrane potential, and increases the input resistance and time constant of the muscle membrane. These results are evidence that neurotrophic control of the frog fast muscle fiber membrane is achieved mainly by substances reaching the muscle via axoplasmic transport and not by the character of the neuronal discharge and motor activity or by synaptic acetylcholine.     

The effects of microtubule dissociating agents on the physiology and cytology of the sensory neuron in the femoral tactile spine of the cockroach, periplaneta americana L

Microtubules are prominent cellular components of the mechanosensory and chemosensory sensilla associated with the insect cuticle, and a range of hypotheses have been proposed to account for their role in sensory transduction. Chemical agents such as colchicine and vinblastine, which dissociate microtubules, also interfere with transduction in these sensilla, and this has been attributed to their anti-microtubule activity. We have now examined the dynamic properties of sensory transduction in the mechanosensitive neuron of the cockroach femoral tactile spine, after the application of colchicine, vinblastine and lumicolchicine. Concurrently we have examined the ultrastructure of the same sensory ending by transmission electron microscopy. All of the drugs reduced the mechanical sensitivity o the receptor. Colchicine and vinblastine achieved this reduction without altering the dynamic properties of the receptor but lumicolchicine changed the dynamic response, and increased the relative sensitivity to rapid movements. Conduction velocity, another measure of neuronal function, which relies upon ionic currents flowing through the membrane, was reduced by all three drugs. The effects of the drugs upon the ultrastructure of the sensory ending were also disparate. In the case of colchicine there was complete dissociation of microtubules in the tubular body and distal dendrite before a total loss of mechanical sensitivity. Vinblastine was less effective in dissociating microtubules, although more effective in the reduction of mechanical sensitivity. With lumicolchicine the dominant morphological effect was a severe disruption of the dendritic membrane. We conclude from these experiments that microtubules are not essential in the transduction of mechanical stimuli by cuticular receptors and that the effects of these drugs upon mechanosensitivity are not directly related to their dissociation of the microtubules in the tubular body, but are more likely to arise from actions upon the cell membrane. These actions could include effects upon tubulin in the membrane or upon other membrane components.     

Semi-linear stochastic models: Computation of moments and conditional moments

In this article we show how linearity with respect to the output of a stochastic dynamic model can be exploited in order to simplify the computation of moments or conditional moments. The results are presented for two examples, one of which includes delays. This feature is often encountered in biological models.     

Generation of an internal matrix in mature avian erythrocyte nuclei during reactivation in cytoplasts

When fused with mouse L-cell cytoplasts, chick erythrocyte nuclei enlarge, take up proteins from the host cytoplasm, and recommence RNA synthesis. We found that during this transition the erythrocyte nuclei gain an internal nuclear matrix, thus providing a novel approach to questions concerning the nature of the salt-resistant intranuclear skeleton. A new method for preparation and examination of the nuclear matrix in situ is also described.     

Partition of unit-copy miniplasmids to daughter cells. I. P1 and F miniplasmids contain discrete, interchangeable sequences sufficient to promote equipartition

Hybrids formed by insertion of the plasmid maintenance regions of P1 or F into a lambda delta att vector form stable unit-copy plasmids in their Escherichia coli host. They must therefore both be substrates for an accurate cellular partition apparatus that ensures that all daughter cells inherit a plasmid copy. Analysis of deletion mutants of both types of hybrid showed that, although the P1 and F plasmid maintenance regions differ in sequence and specificity, they are similar in general organization. Each contains an approximately 3 X 10(3) base-pair region that is essential for replication (rep) and an adjacent but separable 3 X 10(3) base-pair region that is essential for the stability of plasmid maintenance (par). Each par region is thought to specify the recognition of the plasmid as a substrate for equipartition. The deletion mutants provide sources of isolated rep and par sequences from both P1 and F DNA. These elements were then used to construct composite plasmids with novel combinations and arrangements of rep and par sequences. Heterologous constructions containing P1 rep and F par or F rep and P1 par sequences were maintained faithfully. We conclude that par regions are both necessary and sufficient to promote equipartition of replicating plasmid DNA. This activity is exerted only in cis but otherwise seems to be independent of the position or orientation of the par sequences within the DNA. Both P1 and F par regions include DNA sequences (incB of P1, incD of F) that we propose are analogues of the centromeres of eukaryotic chromosomes. The remaining portions of the par regions are known to encode protein products that, we believe, act at the inc sites. Extra copies of these inc sites appear to exert incompatibility by competition for the cellular partition apparatus.     

Crystals of the human heavy chain disease protein Riv and human Fc fragment are isomorphous: further evidence for conformational flexibility in the hinge region of immunoglobulins

Protein Riv is a human gamma 1 heavy chain disease immunoglobulin variant with a deletion of the entire VH and CH1 domains and consisting of most of the hinge region plus the CH2 and CH3 domains. Crystals of this protein are orthorhombic, belonging to the space group P2(1)2(1)2(1), with a = 80.1 A, b = 145.5 A, c = 50.1 A. These crystals are shown to be isomorphous with crystals of a human Fc fragment, indicating that the hinge region and the initial part of the CH2 domain of protein Riv do not assume a unique conformation in the crystalline state.